JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):227
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263855

P-214. Sublingual rescue progesterone for luteal phase support in artificial cycles: A Brazilian case series

Aristides Manoel Bragheto¹, Isabella Carinhani Bragheto¹, Daniel Gustavo Faundes¹

¹ Fivmed - Campinas – SP- Brasil

Objective: To report serum progesterone levels and pregnancy outcomes in the first Brazilian case series of artificial assisted reproduction cycles supplemented with sublingual progesterone lozenges.
Methods: Women who underwent frozen embryo transfer at a private fertility clinic between April 1 and June 30, 2025, with artificial cycles received standard endometrial preparation with oral estradiol valerate (2 mg, TDS), and micronized vaginal progesterone (400 mg, BD), both of which were maintained following embryo transfer until, either, a negative result or 10 weeks gestation. Serum progesterone was measured one day prior to embryo transfer and, if levels were below 10 ng/mL, patients were included and received compounded sublingual micronized progesterone lozenges (200 mg, TDS), immediately after embryo transfer. The first and second post-transfer measurements were performed at 7:00 AM and 3:00 PM on the day after transfer, and the third at 7:00 AM three days after transfer, with all measurements obtained before administration of sublingual progesterone. Primary outcomes included serum progesterone levels and biochemical pregnancy (human chorionic gonadotropin \[hCG]>5 mlU/mL), ongoing pregnancy (pregnancy sustained past 8th week), biochemical miscarriage (per positive hCG), and clinical miscarriage (defined by the loss of a gestational sac or loss of fetal heart rate within the gestational sac). Secondary outcomes analyzed included treatment adherence and adverse effects. Written consent was obtained for all participants.
Results: Twenty-seven women participated in this case series. The mean age was 38.4 (±6.09) years. Mean serum progesterone level before embryo transfer was 7.88 (±2.03) ng/mL. On the first, second, and third post-transfer measurements, levels increased progressively to 31.7 (±31.0), 42.6 (±43.9) and 52.5 (±57.1) ng/mL, respectively. Progesterone measurement was not performed in one participant during the second post-transfer measurement, and in six participants during the third post-transfer measurement. Biochemical pregnancy rates, ongoing pregnancy, biochemical miscarriage, and clinical miscarriage were 81.5%, 77.3%, 18.2%, and 5.5%, respectively. Treatment adherence was optimal, with all participants using the prescribed medication. Only three patients reported drowsiness and one nausea.
Conclusion: Recent studies have shown that inadequate serum progesterone levels on the day of embryo transfer are associated with lower pregnancy rates and an increased risk of miscarriage. As an alternative, rescue progesterone on the day of embryo transfer has been adopted, preferably via intramuscular or subcutaneous routes, avoiding hepatic metabolism and providing more stable hormone levels. However, its use is limited in Brazil due to the need for importation, resulting in high costs, as well as causing significant discomfort. This is the first documented case series describing the use of sublingual rescue progesterone during the luteal phase in artificial assisted reproduction cycles. Serum progesterone levels were measured according to the drug's pharmacokinetics, and in all cases remained above 10 ng/mL throughout the treatment period, thus meeting therapeutic targets while bypassing hepatic metabolism. Adverse effects were minimal with no discontinuation or medical intervention required. Compared with intramuscular or subcutaneous administration, sublingual progesterone is well tolerated, less invasive, and considerably cheaper, with the added advantage of being compounded locally. Pregnancy and miscarriage rates were consistent with published data, indicating comparable efficacy to intramuscular formulations in terms of serum progesterone levels and positive pregnancy test rates. However, this study has limitations, including few cases and small sample size and absence of a control group. Nevertheless, the findings support further investigation through a well-designed non-inferiority randomized trial to confirm the therapeutic equivalence of sublingual progesterone. If validated, this approach could represent a cost-effective and patient-friendly alternative to current standards, potentially influencing clinical practice in assisted reproduction.